Squalene (SQE) is a triterpenoid hydrocarbon oil, C30H50, that is widely produced by both plants and animals, and is present in human food. In humans, SQE serves a as precursor in the synthesis of cholesterol and all of the steroid hormones (Mayes, 1996; Granner, 1996) (FIG. 1). Both SQE and cholesterol are transported in the blood on very low density lipoproteins (VLDL) and low density lipoproteins (LDL) (Miettinen, 1982; Koivisto and Miettinen, 1988). Squalene and cholesterol are also synthesized in the liver and in the epidermis of the skin where SQE comprises a large amount of the oil secreted by sebaceous glands (Stewart, 1992) Because it is a naturally occurring biodegradable oil, SQE, and its hydrogenated derivative squalane, each has been proposed as the oil component of oil-in-water emulsions to be used as new adjuvants for vaccines.
Although not included in any vaccines licensed in the United States, a SQE—containing emulsion is part of an influenza vaccine licensed in Italy and has been given without adverse effects to hundreds of thousands of people (Podda, 2001; Ott et al., 2000). Numerous other human clinical trials for influenza (Ott et al., 2000; Nicholson et al., 2001; Gasparini et al., 2001), cytomegalovirus (Drulak et al., 2000), hepatitis B (Heineman et al., 1999), papillomavirus (Harro et al., 2001), HIV (Kahn et al., 1994; Mitchell et al., 2002; McFarland et al., 2001; Cunningham et al., 2001), and malaria (Stoute et al., 1997; Stoute et al., 1998; Kester et al., 2001; Rickman et al., 1991) have used SQE emulsions. Vaccine reactions were typically mild. However, some moderate to severe reactions, that can be attributed to other adjuvants in the formulations, were reported (Kahn et al., 1994; Rickman et al., 1991; Stoute et al., 1997; Kester et al., 2001). Furthermore, no adverse reactions were reported following intravenous injection of humans with chylomicron-like lipid emulsions containing SQE (Relas et al., 2001).